Mouse Rab11-FIP4 regulates proliferation and differentiation of retinal progenitors in a Rab11-independent manner
Mouse Rab11-FIP4 regulates proliferation and differentiation of retinal progenitors in a Rab11-independent manner
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DOI：
10.1002/dvdy.21009
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发表时间：
2007-01-01
影响因子：
2.5
通讯作者：
Watanabe, Sumiko
中科院分区：
文献类型：
--
作者：
Muto, Akihiko;Aoki, Yutaka;Watanabe, Sumiko
我们确定Rab 11家族相互作用蛋白4（Rab 11-FIP 4）为在发育中的小鼠视网膜中强烈表达的基因。编码全长蛋白的主要转录物mRab 11-FIP 4A主要在神经组织中表达;而编码N-末端截短形式的蛋白的替代转录物mRab 11-FIP 4 B作为次要形式普遍表达。mRab 11-FIP 4A在视网膜中的功能获得促进细胞周期退出，并增加位于内核层的视网膜细胞亚群，如双极细胞和Muller胶质细胞。在功能丧失实验中观察到表型恢复。此外，Shh信号被认为参与了这些功能。使用截短突变体的分析揭示了含有保守EF-手基序的N-末端区域对于由mRab 11-FIP 4A的表达诱导的视网膜表型的重要作用，而与Rab 11的结合是不稳定的，这表明mRab 11-FIP 4A作用在视网膜发育的调节中涉及一种新的Rab 11独立机制。
We identified Rab11-family interacting protein 4 (Rab11-FIP4) as a gene strongly expressed in the developing mouse retina. The major transcript encoding a full-length protein, mRab11-FIP4A, was expressed predominantly in neural tissues; whereas an alternative transcript encoding an N-terminally truncated form of the protein, mRab11-FIP4B, was expressed ubiquitously as a minor form. Gain-of-function of mRab11-FIP4A in retina promoted cell cycle exit and increased subpopulations of retinal cells localized in the inner nuclear layer, such as bipolar cells and Muller glia. Reversal of the phenotype was observed in the loss-of-function experiment. Furthermore, Shh signaling was suggested to be involved in these functions. Analysis using truncation mutants revealed the essential role of the N-terminal region containing a conserved EF-hand motif for the retinal phenotypes induced by the expression of mRab11-FIP4A, whereas binding to Rab11 was dispensable, suggesting the involvement of a novel Rab11-independent mechanism for mRab11-FIP4A action in the regulation of retinal development.